scholarly journals The Extract of Corydalis yanhusuo Prevents Morphine Tolerance and Dependence

2021 ◽  
Vol 14 (10) ◽  
pp. 1034
Author(s):  
Lamees Alhassen ◽  
Khawla Nuseir ◽  
Allyssa Ha ◽  
Warren Phan ◽  
Ilias Marmouzi ◽  
...  

The opioid epidemic was triggered by an overprescription of opioid analgesics. In the treatment of chronic pain, repeated opioid administrations are required which ultimately lead to tolerance, physical dependence, and addiction. A possible way to overcome this conundrum consists of a co-medication that maintains the analgesic benefits of opioids while preventing their adverse liabilities. YHS, the extract of the plant Corydalis yanhusuo, has been used as analgesic in traditional Chinese medicine for centuries. More recently, it has been shown to promote analgesia in animal models of acute, inflammatory, and neuropathic pain. It acts, at least in part, by inhibiting the dopamine D2 receptor, suggesting that it may be advantageous to manage addiction. We first show that, in animals, YHS can increase the efficacy of morphine antinociceptive and, as such, decrease the need of the opioid. We then show that YHS, when coadministered with morphine, inhibits morphine tolerance, dependence, and addiction. Finally, we show that, in animals treated for several days with morphine, YHS can reverse morphine dependence and addiction. Together, these data indicate that YHS may be useful as a co-medication in morphine therapies to limit adverse morphine effects. Because YHS is readily available and safe, it may have an immediate positive impact to curb the opioid epidemic.

2018 ◽  
Vol 17 (1) ◽  
pp. 138-143
Author(s):  
Siti Norhajah Hashim ◽  
Nasir Mohamad ◽  
Zulkifli Mustapha ◽  
Nor Hidayah Abu Bakar ◽  
Rohayah Husain ◽  
...  

Introduction:Honey has been used traditionally in medicine as well as food supplements. Honeybees are said to be able to cure many diseases. However, its influences on opioid tolerance and dependence have not yet been clarified.Materials and Methods:Adult male Sprague- Dawley rats were rendered tolerant to the analgesic effect of morphine by injection of morphine (10 mg/kg, i.p.) twice daily for 14 days. To develop morphine dependence rats given escalating doses of chronic morphine. To determine the effect of stingless bee honey on the development of morphine tolerance and dependence. The hotplate and naloxone precipitation tests were used to assess the degree of tolerance and dependence, respectively.The results: Our results showed that chronic morphine-injected rats displayed tolerance to the analgesic effect of morphine as well as morphine dependence. Methadone+morphine (MetM), methadone+morphine+ honey (MetMH) and morphine+Honey (MH) significantlylower the development of morphine tolerance with p-value p<0.05. In addition, concomitant treatment of morphine with MH and MetMH attenuated almost all of the naloxone-induced withdrawal signs which include abdominal contraction, diarrhea, pertussis, teeth chattering, and jumping.Conclusion: The data indicate that honey has a potential to reduce tolerant and dependence property.Bangladesh Journal of Medical Science Vol.17(1) 2018 p.138-143


2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Daisuke Sato ◽  
Michiko Narita ◽  
Yusuke Hamada ◽  
Tomohisa Mori ◽  
Kenichi Tanaka ◽  
...  

AbstractEmerging evidence suggests that the mesolimbic dopaminergic network plays a role in the modulation of pain. As chronic pain conditions are associated with hypodopaminergic tone in the nucleus accumbens (NAc), we evaluated the effects of increasing signaling at dopamine D1/D2-expressing neurons in the NAc neurons in a model of neuropathic pain induced by partial ligation of sciatic nerve. Bilateral microinjection of either the selective D1-receptor (Gs-coupled) agonist Chloro-APB or the selective D2-receptor (Gi-coupled) agonist quinpirole into the NAc partially reversed nerve injury-induced thermal allodynia. Either optical stimulation of D1-receptor-expressing neurons or optical suppression of D2-receptor-expressing neurons in both the inner and outer substructures of the NAc also transiently, but significantly, restored nerve injury-induced allodynia. Under neuropathic pain-like condition, specific facilitation of terminals of D1-receptor-expressing NAc neurons projecting to the VTA revealed a feedforward-like antinociceptive circuit. Additionally, functional suppression of cholinergic interneurons that negatively and positively control the activity of D1- and D2-receptor-expressing neurons, respectively, also transiently elicited anti-allodynic effects in nerve injured animals. These findings suggest that comprehensive activation of D1-receptor-expressing neurons and integrated suppression of D2-receptor-expressing neurons in the NAc may lead to a significant relief of neuropathic pain.


2020 ◽  
pp. 1-7
Author(s):  
Zeynep Cetin ◽  
Ozgur Gunduz ◽  
Ruhan D. Topuz ◽  
Dikmen Dokmeci ◽  
Hakan C. Karadag ◽  
...  

<b><i>Objective:</i></b> Hydrogen sulfide is an endogenous gaseous mediator that has been indicated to have a role in pain mechanisms. In this study, we aimed to detect brain and spinal cord hydrogen sulfide levels during different phases of tolerance and dependence to morphine and to determine the effects of inhibition of endogenous hydrogen sulfide production on the development of tolerance and dependence. <b><i>Methods:</i></b> Morphine tolerance and dependence was developed by subcutaneous injection of morphine (10 mg/kg) twice daily for 12 days. Physical dependence was determined by counting the jumps for 20 min, which is a withdrawal symptom occurring after a single dose of naloxone (5 mg/kg) administered intraperitoneally (i.p.). Propargylglycine (30 mg/kg, i.p.), a cystathionine-γ-lyase inhibitor, and hydroxylamine (12.5 mg/kg, i.p.), a cystathionine-β-synthase inhibitor, were used as hydrogen sulfide synthase inhibitors. The tail-flick and hot-plate tests were used to determine the loss of antinociceptive effects of morphine and development of tolerance. <b><i>Results:</i></b> It was found that chronic and acute uses of both propargylglycine and hydroxylamine prevented the development of tolerance to morphine, whereas they had no effect on morphine dependence. Chronic and acute administrations of hydrogen sulfide synthase inhibitors did not exert any difference in hydrogen sulfide levels in brain and spinal cords of both morphine-tolerant and -dependent animals. <b><i>Conclusion:</i></b> It has been concluded that hydrogen sulfide synthase inhibitors may have utility in preventing morphine tolerance.


2020 ◽  
Vol 21 (6) ◽  
pp. 1945
Author(s):  
Hiroharu Maegawa ◽  
Nayuka Usami ◽  
Chiho Kudo ◽  
Hiroshi Hanamoto ◽  
Hitoshi Niwa

While the descending dopaminergic control system is not fully understood, it is reported that the hypothalamic A11 nucleus is its principle source. To better understand the impact of this system, particularly the A11 nucleus, on neuropathic pain, we created a chronic constriction injury model of the infraorbital nerve (ION-CCI) in rats. ION-CCI rats received intraperitoneal administrations of quinpirole (a dopamine D2 receptor agonist). ION-CCI rats received microinjections of quinpirole, muscimol [a gamma-aminobutyric acid type A (GABAA) receptor agonist], or neurotoxin 6-hydroxydopamine (6-OHDA) into the A11 nucleus. A von Frey filament was used as a mechanical stimulus on the maxillary whisker pad skin; behavioral and immunohistochemical responses to the stimulation were assessed. After intraperitoneal administration of quinpirole and microinjection of quinpirole or muscimol, ION-CCI rats showed an increase in head-withdrawal thresholds and a decrease in the number of phosphorylated extracellular signal-regulated kinase (pERK) immunoreactive (pERK-IR) cells in the superficial layers of the trigeminal spinal subnucleus caudalis (Vc). Following 6-OHDA microinjection, ION-CCI rats showed a decrease in head-withdrawal thresholds and an increase in the number of pERK-IR cells in the Vc. Our findings suggest the descending dopaminergic control system is involved in the modulation of trigeminal neuropathic pain.


2017 ◽  
Vol 492 (2) ◽  
pp. 269-274 ◽  
Author(s):  
Junfei Zhou ◽  
Fang Wang ◽  
Chang Xu ◽  
Zipeng Zhou ◽  
Wei Zhang

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Wen-Ling Dai ◽  
Feng Xiong ◽  
Bing Yan ◽  
Zheng-Yu Cao ◽  
Wen-Tao Liu ◽  
...  

2018 ◽  
Vol 25 (32) ◽  
pp. 3895-3916 ◽  
Author(s):  
Andrea Bedini ◽  
Santi Spampinato

Background: Chronic pain states are clinically relevant and yet unsolved conditions impacting on quality of life and representing an important social and economic burden; these diseases are poorly treated with the currently available drugs, being urgent the need of innovative analgesics. In this frame, novel analogues of endomorphin-1 and dermorphin emerge as promising starting points to develop innovative, more effective analgesics to treat neuropathic pain. Methods: An extensive and structured search of bibliographic databases for peer-reviewed research literature was undertaken using focused review questions; all the retrieved papers were published on prestigious international journals by the experts of the field and were carefully analyzed to collect all the information and data necessary to the conceptual framework of this review. Results: One hundred papers were included in this review; forty-one defined the up-to-date findings on neuropathic pain etiopathogenesis and its currently available treatment options. Thirty-five papers described all the advantages and drawbacks of using endomorphin-1 (23) or dermorphin (12) in the frame of neuropathic pain and outlined the most relevant advances in developing endomorphin-1 and dermorphin analogs useful as potential, innovative analgesics. Twenty-four papers provided the latest insights into exploiting biased agonism at opioid receptor as an innovative strategy to develop more effective and safer analgesics. Conclusion: This review reports that innovative opioid peptides will be of great help in better understanding the multifaceted scenario of neuropathic pain treatment, providing very interesting opportunities for the identification of novel and more effective opioid analgesics to be employed as medications.


Author(s):  

The use of opioids as an anodyne for chronic pain was not prevalent before the 1980s1. Students in medical schools had learnt to avoid prescribing opioids, considered highly addictive for treatment of non-malignant chronic pain1. Yet, from the early 1990s, prescription opioids emerged as a widely accepted method of treating chronic pain and palliative care2. Previously, chronic pain was treated in multidisciplinary clinics with coordinated care which included physical exams, medication management, biopsychosocial evaluation, cognitive behavioral treatment, physical therapy, and occupational therapy2. Starting in the early 1990’s, under dubious antecedence, opioid analgesics were promoted as the proprietary remedy for chronic pain and received endorsement and support from care providers across the United States3. Non-cancerous chronic pain, as a phenomenon, was thus elevated to an ailment or a medical condition by its own right from its erstwhile status as a corollary to another medical condition. This led to an increase in opioid analgesic prescriptions, followed by a wide-ranging abuse by patients, converting opioid use disorder (OUD) to a problem of epidemic proportions4. Apart from the legal course of action initiated against Perdue Pharma, in 2020, the maker and distributor of Oxycontin that resulted in a $3.8 billion lawsuit settlement, in which Perdue Pharma pleaded guilty; since the recognition of this problem, new measures have been adopted to counter the opioid epidemic by clinicians. There has been a significant shift towards circumvention by physicians prescribing opioids for non-cancerous chronic pain. In a few instances, providers have resorted to putting a temporary moratorium on prescribing opioids to all non-cancerous chronic pain cases5. The Center for Disease Control (CDC) and various state agencies have passed protocols, installed prescription monitoring programs (PMPs), and created taskforces to rein in flagrant prescription practices by medical providers. Mental health counseling and alternative, non-prescriptive pain management procedures have been reintroduced in treatment as a new way of approaching the problem6,7. The Substance Abuse and Mental Health Administration (SAMHSA) have suggested hybrid programs such as medically assisted treatment (MAT) which utilizes the medical approach of prescribing slow releasing drugs with concomitant counseling for patients, as one of the best practices to intervene with opioid use disorders8. An integrated healthcare approach brought primary care physicians, nurses, and physician’s assistants together with addiction counselors and social workers to coordinate and implement treatment for opioid misuse9,10. These new approaches are laudable and effective, yet we argue, in this paper, for ascertaining the treatment of chronic pain as a co-occurring disorder to addiction. While acknowledging the two original transgressions of the opioid epidemic: a) the delineation and decontextualization of chronic pain as an independent medical phenomenon, and b) the over-prescription of opioid analgesics to treat chronic pain; we argue that recognizing chronic pain as a co-occurring disorder with addiction and psychological trauma could help providers contextualize it better, leading to an improved treatment protocol. Over last two decades, persistent over-prescribing has set forth a culture of righteous demand among patients to obtain opioids and receive instant pharmacological sedation as an antidote to chronic pain. This culture, which may have taken roots, could cause resistance among chronic pain patients towards any change to alternative treatment plans. This could frustrate medical providers and reformers as they usher in the new treatment procedures promulgated by SAMHSA and the CDC. Thus, a co-occurring diagnostic framework could provide a pathway to better understand this treatment dilemma. The co-occurring disorder lens of diagnosis could provide a pathway to understand this treatment dilemma. In this paper, we do a critical, non-systematic review of existing literature that explores the intersection of chronic pain and OUD to make a case that these issues should be treated as co-occurring disorders and not as disconnected, independent phenomenon. We review the scope of the problem and provide an analysis of the complex relationship between chronic pain and usage of opioids from both pharmacological and psychological viewpoints and explore the challenges to treatment. We take an ecological and exchange theory perspective to understand the co-occurrence of pain and opioids addiction from a trauma-informed lens to unpack the complexity that OUD poses in juxtaposition to chronic pain. Furthermore, we explore the strategies to develop an integrated healthcare workforce from a co-occurring disorder perspective. Furthermore, we explain the context of co-occurring pain, addiction, and psychological trauma and identify the pertinent questions that such co-occurrences pose for treatment protocols. We draw our argument from a critical review of the literature as well as the incidence and prevalence of OUD.


Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6168
Author(s):  
Kornél Király ◽  
Dávid Á. Karádi ◽  
Ferenc Zádor ◽  
Amir Mohammadzadeh ◽  
Anna Rita Galambos ◽  
...  

The current protocols for neuropathic pain management include µ-opioid receptor (MOR) analgesics alongside other drugs; however, there is debate on the effectiveness of opioids. Nevertheless, dose escalation is required to maintain their analgesia, which, in turn, contributes to a further increase in opioid side effects. Finding novel approaches to effectively control chronic pain, particularly neuropathic pain, is a great challenge clinically. Literature data related to pain transmission reveal that angiotensin and its receptors (the AT1R, AT2R, and MAS receptors) could affect the nociception both in the periphery and CNS. The MOR and angiotensin receptors or drugs interacting with these receptors have been independently investigated in relation to analgesia. However, the interaction between the MOR and angiotensin receptors has not been excessively studied in chronic pain, particularly neuropathy. This review aims to shed light on existing literature information in relation to the analgesic action of AT1R and AT2R or MASR ligands in neuropathic pain conditions. Finally, based on literature data, we can hypothesize that combining MOR agonists with AT1R or AT2R antagonists might improve analgesia.


2020 ◽  
Vol 48 (5) ◽  
pp. 030006052090365
Author(s):  
Razia Abdool Gafaar Khammissa ◽  
Raoul Ballyram ◽  
Jeanine Fourie ◽  
Michael Bouckaert ◽  
Johan Lemmer ◽  
...  

Pain induced by inflammation and nerve injury arises from abnormal neural activity of primary afferent nociceptors in response to tissue damage, which causes long-term elevation of the sensitivity and responsiveness of spinal cord neurons. Inflammatory pain typically resolves following resolution of inflammation; however, nerve injury—either peripheral or central—may cause persistent neuropathic pain, which frequently manifests as hyperalgesia or allodynia. Neuralgias, malignant metastatic bone disease, and diabetic neuropathy are some of the conditions associated with severe, often unremitting chronic pain that is both physically and psychologically debilitating or disabling. Therefore, optimal pain management for patients with chronic neuropathic pain requires a multimodal approach that comprises pharmacological and psychological interventions. Non-opioid analgesics (e.g., paracetamol, aspirin, or other non-steroidal anti-inflammatory drugs) are first-line agents used in the treatment of mild-to-moderate acute pain, while opioids of increasing potency are indicated for the treatment of persistent, moderate-to-severe inflammatory pain. N-methyl D-aspartate receptor antagonists, antidepressants, anticonvulsants, or a combination of these should be considered for the treatment of chronic neuropathic pain. This review discusses the various neural signals that mediate acute and chronic pain, as well as the general principles of pain management.


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